Chemotherapy Chemistry Seminar

Question 1

Describe the MoA of alkylating agent

Answer 1

Form highly reactive aziridinium ion that can be attacked by nucleophilic DNA bases, guanine
Alkyl groups are transferred to nucleophilic sites of DNA bases
Can occur twice leading to cross-linked DNA
Damage caused cannot be repaired = cancer cells can no longer proliferate

Question 2

How do intercalating agents work?

Answer 2

Able to insert themselves into space between successive DNA base pairs
= slight unwinding of DNA helix alternating DNA structure
= causes cells to die

Question 3

What is important about the chemical structure of intercalating agents for their MoA?

Answer 3

Planar aromatic rings

Question 4

What is the role of topoisomerase enzymes?

Answer 4

Key role in DNA replication, transcription, chromosome separation + DNA repair

Question 5

What is the MoA of Etoposide (topoisomerase inhibitor (poison)?

Answer 5

Poison = STOP promptly
Stabilises covalent intermediate between DNA + topoisomerase II
= DNA strands NOT re-joined
= damage causes cytotoxic effect

Question 6

What are 3 drugs known to methylate O6-position of guanine?

Answer 6

Procarbazine, dacarbazine + temozolomide

Question 7

Why is O6-methylation of guanine cytotoxic?

Answer 7

O6-methylguanine preferentially pairs with thymine
= mispair = G-C
= mutation = cell destruction

Question 8

How do antimetabolites work?

Answer 8

Are false substrates for critical nucleotide biosynthesis enzymes
= block the synthesis of DNA nucleotides + reduce tumour growth

Question 9

What are examples of antimetabolites?

Answer 9

Pyrimidine antagonists = fluorouracil, capecitabine
Purine antagonists = mercaptopurine, thioguanine
Folate antagonists = methotrexate (pemetrexed (methotrexate analogue))

Question 10

Describe the MoA of vinca alkaloids
KNOW THIS

Answer 10

Microtubule destabilising agents
Block tubulin polymerisation by binding at the interface of 2 tubulin heterodimers + inhibit uptake of GPT, which is essential for microtubule elongation
= mitotic spindle cannot be formed
= prevent cells from undergoing mitosis
= unable to replicate
Work in metaphase

Question 11

Describe the MoA of Paclitaxel (taxanes)

Answer 11

Microtubule stabilising agents
Promote microtubule polymerisation
= mitotic spindle doesn’t breakdown + cells arrested in mitosis
= unable to replicate
Work in metaphase